Molecular–cytogenetic characterization of the origin and the presence of pericentromeric euchromatin on minute supernumerary marker chromosomes (SMCs)

Liehr, Thomas; Hickmann, G; Kozlowski, P.; Claussen, Uwe; Starke, Heike

doi:10.1023/b:chro.0000021916.18019.1c

Cited by 10 publications

(8 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Various phenotypic consequences of sSMCs are due to different chromosomal origin, euchromatin content, size, mosaicism, parental origin, potential of genomic imprinting effects, homozygosity of autosomal recessive mutations (in the case of isodisomy), and sex of sSMC carriers (Buckton 1985;Webb 1994;Crolla 1998;Langer et al 2001;Kotzot 2002;Liehr et al 2004a;Liehr et al 2004c;Crolla et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Pietrzak¹,

Mrasek

Obersztyn³

et al. 2007

J Appl Genet

View full text Add to dashboard Cite

Small supernumerary marker chromosomes (sSMCs) are a morphologically heterogeneous group of additional structurally abnormal chromosomes that cannot be identified unambiguously by conventional banding techniques alone. Molecular cytogenetic methods enable detailed characterization of sSMCs; however, in many cases interpretation of their clinical significance is problematic. The aim of our study was to characterize precisely sSMCs identified in three patients with dysmorphic features, psychomotor retardation and multiple congenital anomalies. We also attempted to correlate the patients' genotypes with phenotypes by inclusion of data from the literature. The sSMCs were initially detected by G-banding analysis in peripheral blood lymphocytes in these patients and were subsequently characterized using multicolor fluorescence in situ hybridization (M-FISH), (sub)centromere-specific multicolor FISH (cenM-FISH, subcenM-FISH), and multicolor banding (MCB) techniques. Additionally, the sSMCs in two patients were also studied by hybridization to whole-genome bacterial artificial chromosome (BAC) arrays (array-CGH) to map the breakpoints on a single BAC clone level. In all three patients, the chromosome origin, structure, and euchromatin content of the sSMCs were determined. In patient RS, only a neocentric r(2)(q35q36) was identified. It is a second neocentric sSMC(2) in the literature and the first marker chromosome derived from the terminal part of 2q. In the other two patients, two sSMCs were found, as M-FISH detected additional sSMCs that could not be characterized in G-banding analysis. In patient MK, each of four cell lines contained der(4)(:p11.1-->q12:) accompanied by a sSMC(18): r(18)(:p11.2-->q11.1::p11.2-->q11.1:), inv dup(18)(:p11.1-->q11.1::q11.1-->p11.1:), or der(18) (:p11.2-->q11.1::q11.1-->p11.1:). In patient NP, with clinical features of trisomy 8p, three sSMCs were characterized: r(8)(:p12-->q11.1::q11.1-->p21:) der(8) (:p11.22-->q11.1::q11.1-->p21::p21-->p11.22:) and der(21)(:p11.1-->q21.3:). The BAC array results confirmed the molecular cytogenetic results and refined the breakpoints to the single BAC clone resolution. However, the complex mosaic structure of the marker chromosomes derived from chromosomes 8 and 18 could only be identified by molecular cytogenetic methods. This study confirms the usefulness of multicolor FISH combined with whole-genome arrays for comprehensive analyses of marker chromosomes.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Pietrzak¹,

Mrasek

Obersztyn³

et al. 2007

J Appl Genet

View full text Add to dashboard Cite

show abstract

“…sSMCs can be recognized as inverted duplicated chromosomes, minute chromosomes, ring or deleted chromosomes, being the mechanism of formation different in each case. sSMCs cell lines have been reported in mosaic with 46 normal chromosomes and numerically abnormal or structurally abnormal balanced karyotypes [6,8]. Phenotypes associated with sSMCs are highly variable (Table 1).…”

Section: Introductionmentioning

confidence: 99%

“…Besides the chromosomal imbalance there are other factors that influence phenotype, such as the level of mosaicism [6]. Mosaicism of sSMC 14 has been reported in about 32 patients; in some cases presenting with clinical features that can include: short stature, mental retardation, microcephaly, hypoplastic alae nasi, midface hypoplasia, exophthalmos, bilateral myopia, retinal microangiopathy, cleft lip and palate, congenital malformation of pancreas, secondary cardiomyopathy, hypogonadism and club feet (Table 1) [8,9]. Furthermore, trisomy 14 in mosaic can also be influenced by uniparental disomy (UPD).…”

Section: Introductionmentioning

confidence: 99%

Partial and complete trisomy 14 mosaicism: clinical follow-up, cytogenetic and molecular analysis

et al. 2014

View full text Add to dashboard Cite

BackgroundTrisomy 14 mosaicism is a rare chromosomal abnormality. It is associated with multiple congenital anomalies. We report a 15 year-old female with an unusual karyotype with three cell lines: 47,XX,+mar/47,XX,+14/46,XX. At six months old she had short stature, cleft palate, hyperpigmented linear spots in arms and legs and developmental delay. At present, she has mild facial dysmorphism and moderate mental retardation.MethodsCytogenetic analysis was performed in peripheral blood lymphocytes and in the light and dark skin following standard methods. DNAarray – Oligo 180 k was carried out using Agilent Technologies and FISH analysis was accomplished using DNA BACs probes to confirm the result obtained by DNAarray. Methylation-Specific PCR (MS-PCR) of the MEG3 promoter and microsatellite analysis were performed.ResultsMicroarray analysis confirmed partial trisomy 14 mosaicism; the marker chromosome was found to be from chromosome 14, the result was confirmed with FISH. Methylation (14q32.3) and microsatellite (14q11-14q32.33) analysis were carried out and UPD was discarded. The global result was: mos 47,XX,+del(14)(q11.2)[45]/47,XX,+14[10]/46,XX[45].ConclusionsThis is a unique case because of the coexistence of two abnormal cell lines, including one with +14 and another with +del(14)(q11.2). To our knowledge, only three patients have been reported with trisomy 14 and another abnormal cell line. The array analysis identified the marker chromosome and characterized the breakpoint. The del(14)(q11.2) does not seem to be related to any particular phenotypic characteristic of the patient; the clinical features of our patient observed until now, can be attributed to trisomy 14 mosaicism. Nevertheless, we cannot discard the manifestation of new symptoms related to her karyotype in the future.Electronic supplementary materialThe online version of this article (doi:10.1186/s13039-014-0065-8) contains supplementary material, which is available to authorized users.

show abstract

“…Early reports of prenatally ascertained minSMC provided no identifi cation or further characterization of the minSMC [7] . More recent reports of prenatal min-SMC incorporated identifi cation and assessment of euchromatin content for prediction of phenotype [8][9][10][11][12][13][14] . In this communication, we describe 11 new cases of prenatal diagnosis of minSMC.…”

Section: Introductionmentioning

confidence: 99%

Prenatal Diagnosis of Minute Supernumerary Marker Chromosomes

Cotter¹,

Drexler

Corley³

et al. 2005

Gynecol Obstet Invest

View full text Add to dashboard Cite

The identification of supernumerary marker chromosomes (SMC) at prenatal diagnosis is problematic, particularly for the prediction of phenotype. The assessment of phenotypic risk is based on the size, morphology and origin of the SMC. Fluorescence in situ hybridization (FISH) characterization and family studies are also employed to aid in determining the significance of a prenatally ascertained SMC. Generally, SMC containing euchromatin are more likely to be associated with abnormal phenotypes and SMC without euchromatin are more likely to result in normal phenotypes. The smallest of SMC, minute SMC (minSMC) appear as dot-like or centric fragments and are particularly difficult to identify and characterize. Previous empirical observations suggested that the risk of phenotypic abnormality in prenatally ascertained minSMC was ≤5%. We identified minSMC in chorionic villus samples (CVS) or amniocytes from 11 unrelated pregnancies. The chromosomal origin of each minSMC was identified by sequential FISH analysis with chromosome-specific centromere probes. Further FISH analysis with whole chromosome paint probes was undertaken to assess each minSMC for the presence or absence of euchromatin, since the presence of euchromatin may be associated with a higher risk of abnormality. Two minSMC were shown to have euchromatin. The first, a minSMC(12) was found in CVS but not confirmed in amniocytes, indicating confined placental mosaicism. The second, a minSMC derived from chromosome 19, was associated with ultrasound abnormalities. Apart from a case with mild speech delay, the remaining minSMC cases without detectable euchromatin had a normal outcome at birth and/or on longer term follow-up. Additional FISH analyses with a telomeric repeat probe showed no signal on any of the minSMC tested, suggesting that they were ring chromosomes in structure. These data further support the concept that minSMC containing euchromatin are more likely to be associated with an abnormal phenotype, although as more data are collected, this may vary by chromosome of origin. The absence of detectable euchromatin, while not guaranteeing a normal result, is most likely to have a normal outcome. The present report and previous studies do not yet allow any significant adjustment of the empirical ≤5% risk estimate for minSMC identified at prenatal diagnosis. However, reporting of additional cases with characterization of the minSMC and particularly with long-term follow-up will, in time, allow for more accurate risk estimates and provide prognostic information.

show abstract

Molecular–cytogenetic characterization of the origin and the presence of pericentromeric euchromatin on minute supernumerary marker chromosomes (SMCs)

Cited by 10 publications

References 23 publications

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Molecular cytogenetic characterization of eight small supernumerary marker chromosomes originating from chromosomes 2, 4, 8,18, and 21 in three patients

Partial and complete trisomy 14 mosaicism: clinical follow-up, cytogenetic and molecular analysis

Prenatal Diagnosis of Minute Supernumerary Marker Chromosomes

Contact Info

Product

Resources

About